Chen H, Sandler D P, Taylor J A, Shore D L, Liu E, Bloomfield C D, Bell D A
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Lancet. 1996 Feb 3;347(8997):295-7. doi: 10.1016/s0140-6736(96)90468-7.
The glutathione S-transferases (GST) mediate exposure to various cytotoxic and genotoxic agents, including those associated with increased risk of the myelodysplastic syndromes (MDS). Both GST M1 (GSTM1) and GST theta 1 (GSTT1) genes have a "null" variant allele, in which the entire gene is absent. We tested whether the homozygous null genotype of GSTM1 and GSTT1 altered the risk for MDS.
In a hospital-based case-control study we analysed lymphocyte or bone-marrow DNA samples from 96 patients with MDS and 201 cancer-free controls of similar age, race, and sex. We have restricted our report to the 92 white MDS patients. We analysed GSTM1 and GSTT1 genotypes by PCR.
The frequency of the GSTT1 null genotype was higher among MDS cases (46%) than among controls (16%). Inheritance of the GSTT1 null genotype conferred a 4.3-fold of MDS (odds ratio 4.3, 95% CI 2.5-7.4, p < 0.00001). The GSTM1 null genotype was not associated with increased risk of MDS (odds ratio 0.8, 0.5-1.3).
Individuals with the GSTT1 null genotype may have enhanced susceptibility to MDS. The mechanism might involve decreased detoxification of environmental or endogenous carcinogens.
谷胱甘肽S-转移酶（GST）介导机体暴露于各种细胞毒性和基因毒性物质，包括那些与骨髓增生异常综合征（MDS）风险增加相关的物质。GST M1（GSTM1）基因和GSTθ1（GSTT1）基因均有一个“无效”变异等位基因，即整个基因缺失。我们检测了GSTM1和GSTT1的纯合无效基因型是否会改变MDS的发病风险。
在一项基于医院的病例对照研究中，我们分析了96例MDS患者以及201例年龄、种族和性别相近的无癌对照者的淋巴细胞或骨髓DNA样本。我们将报告限定于92例白人MDS患者。我们通过聚合酶链反应（PCR）分析GSTM1和GSTT1基因型。
MDS病例中GSTT1无效基因型的频率（46%）高于对照组（16%）。GSTT1无效基因型的遗传使患MDS的风险增加4.3倍（比值比4.3，95%可信区间2.5 - 7.4，p < 0.00001）。GSTM1无效基因型与MDS风险增加无关（比值比0.8，0.5 - 1.3）。
GSTT1无效基因型个体可能对MDS易感性增强。其机制可能涉及环境或内源性致癌物解毒能力下降。
